Mammalian Taste Bud Cells Utilize Extragemmal 5-Hydroxy-L-Tryptophan to Biosynthesize the Neurotransmitter Serotonin

Abstract

Serotonin or 5-hydroxytryptamine (5-HT) is an important neurotransmitter that is found in mammalian taste buds and can regulate the output of intragemmal signaling networks onto afferent nerve fibers. However, it is unclear how 5-HT is produced, synthesized locally inside taste buds or absorbed from outside sources. In this study, we attempt to address this question by delineating the process of possible 5-HT biosynthesis within taste buds. First, we verified that the rate-limiting enzyme tryptophan hydroxylase (TPH2) responsible for converting L-tryptophan into the intermediate 5-hydroxy-L-tryptophan (5-HTP) is expressed in a subset of type II taste bud cells (TBCs) whereas the enzyme aromatic L-aromatic amino acid decarboxylase (AADC) capable of converting 5-HTP into 5-HT is found in type III TBCs. And abolishment of TPH2 did not affect the production of intragemmal 5-HT or alter TBCs; the mutant mice did not show any changes in behavioral responses to all five primary taste qualities: sweet, umami, bitter, salty, and sour. Then we identified that 5-HTP as well as AADC are abundant in type III TBCs; and application of an AADC inhibitor significantly blocked the production of 5-HT in taste buds. In contrast, administration of an inhibitor on serotonin-reuptake transporters had minimal impact on the 5-HT amount in taste buds, indicating that exogenous 5-HT is not a major source for the intragemmal transmitter. Taken together, our data indicate that intragemmal serotonin is not biosynthesized de novo from tryptophan; instead, it is produced by AADC-mediated conversion of 5-HTP absorbed from the plasma and/or nerve fibers into 5-HT. Thus, our results suggest that the overall bodily 5-HTP level in the plasma and nervous system can regulate taste buds’ physiological function, and provide an important molecular mechanism connecting these peripheral taste organs with the circulatory and nervous systems.

Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform

“…The reduction of DDC expression by SARS-CoV2, which results in hampered biosynthesis of the neurotransmitters dopamine and serotonin, provides insight in the cause of the neurological manifestations frequently observed in these patients. In line with this, previous data on the crucial role of DDC-dependent synthesis of serotonin in taste bud cells for normal taste functions [56] might explain the high incidence of smell and/or taste loss in patients [57]. Moreover, serotonin has been shown to exert functions in innate as well as adaptive immunity, [58] thus a putative SARS-CoV-2-mediated deregulation of its production may be extremely beneficial for the virus.…”

Causes of hypogeusia/hyposmia in SARS‐CoV2 infected patients

“…13 ACE2 and DDC are expressed by murine taste buds 14 and the DDC-dependent synthesis of serotonin was found to be mandatory for normal taste functions. 15 Besides the hypothesis of a cytopathic effect on neurosensory cells, the high incidence of smell and/or taste loss in COVID-19 patients might thus reflect the impact of SARS-Cov2 on the synthesis of neurotransmitters (notably serotonin and dopamine) by ACE2expressing cells.…”

Salty taste enhancement of rosemary water extract in mouse and human

“…Currently, among the five basic tastes, sweet, umami, and bitter are thought to be accepted by type II, sour by type III, and salty by type III. Type III taste cells synapse with taste nerve fibers expressing serotonin receptors, and express aromatic Lamino acid decarboxylase (AroDC) [7], which catalyzes the production of serotonin [8]. Some previous studies have suggested that serotonin released from taste buds activates serotonin receptors on taste nerve fibers to facilitate taste signaling [9,10].…”